3-O-tert-butyl 4-O-methyl (1S,4R,6S,7Z,14S,18S)-14-(cyclopentyloxycarbonylamino)-18-(4-nitrobenzoyl)oxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-3,4-dicarboxylate | 928760-42-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-O-tert-butyl 4-O-methyl (1S,4R,6S,7Z,14S,18S)-14-(cyclopentyloxycarbonylamino)-18-(4-nitrobenzoyl)oxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-3,4-dicarboxylate
• CAS: 928760-42-3
• 化学式: C₃₇H₄₈N₄O₁₂
• 分子量: 740.808
• InChiKey: YWSLQOBSTQDJHT-FVKWPPQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  53
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  204
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  3-O-tert-butyl 4-O-methyl (1S,4R,6S,7Z,14S,18S)-14-(cyclopentyloxycarbonylamino)-18-(4-nitrobenzoyl)oxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-3,4-dicarboxylate 在 苯磺酸 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以95%的产率得到(1S,4R,6S,7Z,14S,18S)-14-cyclopentyloxycarbonylamino-18-(4-nitro-benzoyloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester
  参考文献：
  名称：

  RCM Macrocyclization Made Practical:  An Efficient Synthesis of HCV Protease Inhibitor BILN 2061

  摘要：

  We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using H-1 NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate.

  DOI：

  10.1021/ol800183x
• 作为产物：
  描述：

  [(3S,5S)-1-[(2S)-2-(cyclopentyloxycarbonylamino)non-8-enoyl]-5-[[(1R,2S)-2-ethenyl-1-methoxycarbonylcyclopropyl]-[(2-methylpropan-2-yl)oxycarbonyl]carbamoyl]pyrrolidin-3-yl] 4-nitrobenzoate 在 1,3-bis-(2,4,6-trimethylphenyl)-2-(imidazolidinylidene)dichloro(5-nitro-2-isopropoxyphenylmethylene)ruthenium 作用下， 以 甲苯 为溶剂， 以6.92 g的产率得到3-O-tert-butyl 4-O-methyl (1S,4R,6S,7Z,14S,18S)-14-(cyclopentyloxycarbonylamino)-18-(4-nitrobenzoyl)oxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-3,4-dicarboxylate
  参考文献：
  名称：

  RCM Macrocyclization Made Practical:  An Efficient Synthesis of HCV Protease Inhibitor BILN 2061

  摘要：

  We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using H-1 NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate.

  DOI：

  10.1021/ol800183x

文献信息

• RCM Macrocyclization Made Practical:  An Efficient Synthesis of HCV Protease Inhibitor BILN 2061
  作者：Chutian Shu、Xingzhong Zeng、Ming-Hong Hao、Xudong Wei、Nathan K. Yee、Carl A. Busacca、Zhengxu Han、Vittorio Farina、Chris H. Senanayake

  DOI：10.1021/ol800183x

  日期：2008.3.1

  We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using H-1 NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate.